Effects of Combining Coronary Calcium Score With Treatment on Plaque Progression in Familial Coronary Artery Disease

Importance: Coronary artery calcium (CAC) scoring provides prognostic information, especially in patients at intermediate risk for coronary artery disease (CAD). However, the benefit of combining CAC score with a primary prevention strategy has not been tested in a randomized trial. Objective: To assess whether combining the CAC score with a prevention strategy can be used to limit plaque progression in intermediate-risk patients with a family history of premature CAD. Design, Setting, and Participants: Prospective, randomized, open-blinded end point clinical trial in 7 hospitals across Australia (between 2013 and 2020; the last date of follow-up was June 5, 2021). Asymptomatic people aged 40 to 70 years with a first-degree relative with CAD onset at younger than 60 years old or second-degree relative with onset at younger than 50 years old were recruited from the community. Interventions: Intermediate-risk participants underwent CAC scoring. Those with a CAC score greater than 0 but less than 400 underwent coronary computed tomography angiography (CCTA) and were randomized to CAC score-informed prevention or usual care. Main Outcomes and Measures: Follow-up CCTA was obtained at 3 years, with plaque volume measured by an independent core laboratory. The primary outcome was total plaque volume, with further analysis for calcified and noncalcified plaque volume. Results: This study included 365 participants (mean [SD] age, 58 [6] years; 57.5% male); 179 in the CAC score-informed and 186 in the usual care groups. Compared with usual care, the CAC score-informed group showed a sustained reduction in total (mean [SD], -3 [31] mg/dL vs -56 [38] mg/dL; P < .001) and LDL (mean [SD], -2 [31] vs -51 [36] mg/dL; P < .001) cholesterol levels at 3 years, which was associated with a reduction in pooled cohort equation risk calculation (mean [SD], 2.1% [2.9%] vs 0.5% [2.9%]; P < .001). Plaque progression was greater in usual care than CAC score-informed participants for total plaque volume (mean [SD], 24.9 [37.7] mm3 vs 15.4 [30.9] mm3; P = .009), noncalcified plaque volume (mean [SD], 15.7 [32.2] mm3 vs 5.6 [28.5] mm3; P = .002), and fibrofatty and necrotic core plaque volume (mean [SD], 4.5 [25.8] mm3 vs -0.8 [12.6] mm3; P = .02). These plaque volume changes were independent of other risk factors including baseline plaque volume, blood pressure, and lipid profile. Conclusions and Relevance: The combination of CAC score with a primary prevention strategy in intermediate-risk patients with a family history of CAD was associated with reduction of atherogenic lipids and slower plaque progression compared with usual care. These data support the use of CAC score to assist intensive preventive strategies in intermediate-risk patients. Trial Registration: anzctr.org.au Identifier: ACTRN12614001294640.